Eukaryotic cells are subdivided by membranes into multiple functionally distinct compartments that are referred to as organelles. Each organelle includes proteins essential for its proper function. These proteins can include sequence motifs often referred to as sorting signals. The sorting signals can aid in targeting the proteins to their appropriate cellular organelle(s). In addition, sorting signals can direct some proteins to be exported, or secreted, from the cell.
One type of sorting sequence is a signal sequence (also referred to as a signal peptide or leader sequence). The signal sequence is present as an amino terminal extension on a newly synthesized polypeptide chain. A signal sequence targets proteins to an intracellular organelle called the endoplasmic reticulum (ER).
The signal peptide takes part in an array of protein-protein and protein-lipid interactions that result in translocation of a polypeptide containing the signal sequence through a channel in the ER. After translocation, a membrane-bound enzyme (signal peptidase) liberates the mature protein from the signal sequence.
The ER functions to separate membrane-bound proteins and secreted proteins from proteins that remain in the cytoplasm. Once targeted to the ER, both secreted and membrane-bound proteins can be further distributed to another cellular organelle called the Golgi apparatus. The Golgi directs the proteins to vesicles, lysosomes, the plasma membrane, mitochondria and other cellular organelles.
Only a limited number of genes encoding human membrane-bound and secreted proteins have been identified. Examples of known secreted proteins include human insulin, interferon, interleukins, transforming growth factor-beta, human growth hormone, erythropoietin, lymphokines. A need exists for identifying and characterizing additional novel human secreted proteins and the genes that encode them.